Functional ultrasound imaging of the human spinal cord.

Utilizing the first in-human functional ultrasound imaging (fUSI) of the spinal cord, we demonstrate the integration of spinal functional responses to electrical stimulation. We record and characterize the hemodynamic responses of the spinal cord to a neuromodulatory intervention commonly used for treating pain and increasingly used for the restoration of sensorimotor and autonomic function. We found that the hemodynamic response to stimulation reflects a spatiotemporal modulation of the spinal cord circuitry not previously recognized. Our analytical capability offers a mechanism to assess blood flow changes with a new level of spatial and temporal precision in vivo and demonstrates that fUSI can decode the functional state of spinal networks in a single trial, which is of fundamental importance for developing real-time closed-loop neuromodulation systems. This work is a critical step toward developing a vital technique to study spinal cord function and effects of clinical neuromodulation.

Heat impacts on human health in the Western Pacific Region: an umbrella review.

Background: High temperatures and heatwaves are occurring more frequently and lasting longer because of climate change. A synthesis of existing evidence of heat-related health impacts in the Western Pacific Region (WPR) is lacking. This review addresses this gap. Methods: The Scopus and PubMed databases were searched for reviews about heat impacts on mortality, cardiovascular morbidity, respiratory morbidity, dehydration and heat stroke, adverse birth outcomes, and sleep disturbance. The last search was conducted in February 2023 and only publications written in English were included. Primary studies and reviews that did not include specific WPR data were excluded. Data were extracted from 29 reviews. Findings: There is strong evidence of heat-related mortality in the WPR, with the evidence concentrating on high-income countries and China. Associations between heat and cardiovascular or respiratory morbidity are not robust. There is evidence of heat-related dehydration and stroke, and preterm and still births in high-income countries in the WPR. Some evidence of sleep disturbance from heat is found for Australia, Japan and China. Interpretation: Mortality is by far the most studied and robust health outcome of heat. Future research should focus on morbidity, and lower income countries in continental Asia and Pacific Island States, where there is little review-level evidence. Funding: Funded by the World Health Organization WPR Office.

Optimal heat stress metric for modelling heat-related mortality varies from country to country.

Combined heat and humidity is frequently described as the main driver of human heat-related mortality, more so than dry-bulb temperature alone. While based on physiological thinking, this assumption has not been robustly supported by epidemiological evidence. By performing the first systematic comparison of eight heat stress metrics (i.e., temperature combined with humidity and other climate variables) with warm-season mortality, in 604 locations over 39 countries, we find that the optimal metric for modelling mortality varies from country to country. Temperature metrics with no or little humidity modification associates best with mortality in ~40% of the studied countries. Apparent temperature (combined temperature, humidity and wind speed) dominates in another 40% of countries. There is no obvious climate grouping in these results. We recommend, where possible, that researchers use the optimal metric for each country. However, dry-bulb temperature performs similarly to humidity-based heat stress metrics in estimating heat-related mortality in present-day climate.

Do temperature changes cause eczema flares? An English cohort study.

BACKGROUND: It is unclear if ambient temperature changes affect eczema. It is also unclear if people with worse disease are more susceptible to weather-related flares, or specific types of emollient offer protection. OBJECTIVES: To investigate the effect of short-term temperature variations on eczema symptoms in children. METHODS: Data from a UK cohort of 519 children with eczema were combined with data from the Hadley Centre's Integrated Surface Database. Hot and cold weeks were defined by average regional temperature > 75th or < 25th percentile, January 2018 to February 2020. Eczema flares were defined as ≥ 3-point change in Patient-Oriented Eczema Measure (POEM). Random-effects logistic regression models were used to estimate the odds ratios of flares in hot and cold weeks (reference group: temperate weeks). RESULTS: The baseline mean age was 4.9 years (SD 3.2) and the POEM score was 9.2 (SD 5.5). From the 519 participants, there were 6796 consecutively paired POEMs and 1082 flares. Seasonal variation in POEM scores was observed, suggesting symptoms worsening in winter and improving in summer. Odds ratios of flares were: 1.15 [95% confidence interval (CI) 0.96-1.39, P = 0.14] in cold weeks and 0.85 (95% CI 0.72-1.00, P = 0.05) in hot weeks. The likelihood ratio test showed no evidence of this differing by disease severity (P = 0.53) or emollient type used (P = 0.55). CONCLUSIONS: Our findings are consistent with previous studies demonstrating either improvements in eczema symptoms or reduced flares in hot weather. Worse disease and different emollient types did not increase susceptibility or provide protection against temperature changes. Further work should investigate the role of sunlight, humidity, pollution and other environmental factors.

The 2021 western North America heat wave among the most extreme events ever recorded globally.

In June 2021, western North America experienced a record-breaking heat wave outside the distribution of previously observed temperatures. While it is clear that the event was extreme, it is not obvious whether other areas in the world have also experienced events so far outside their natural variability. Using a novel assessment of heat extremes, we investigate how extreme this event was in the global context. Characterizing the relative intensity of an event as the number of standard deviations from the mean, the western North America heat wave is remarkable, coming in at over four standard deviations. Throughout the globe, where we have reliable data, only five other heat waves were found to be more extreme since 1960. We find that in both reanalyses and climate projections, the statistical distribution of extremes increases through time, in line with the distribution mean shift due to climate change. Regions that, by chance, have not had a recent extreme heat wave may be less prepared for potentially imminent events.

Estimating heat-related mortality in near real time for national heatwave plans.

Heatwaves are a serious threat to human life. Public health agencies that are responsible for delivering heat-health action plans need to assess and reduce the mortality impacts of heat. Statistical models developed in epidemiology have previously been used to attribute past observed deaths to high temperatures and project future heat-related deaths. Here, we investigate the novel use of summer temperature-mortality associations established by these models for monitoring heat-related deaths in regions in England in near real time. For four summers in the period 2011-2020, we find that coupling these associations with observed daily mean temperatures results in England-wide heatwave mortality estimates that are consistent with the excess deaths estimated by UK Health Security Agency. However, our results for 2013, 2018 and 2020 highlight that the lagged effects of heat and characteristics of individual summers contribute to disagreement between the two methods. We suggest that our method can be used for heatwave mortality monitoring in England because it has the advantages of including lagged effects and controlling for other risk factors. It could also be employed by health agencies elsewhere for reliably estimating the health burden of heat in near real time and near-term forecasts.

Expression and immunogenicity of secreted forms of bovine ephemeral fever virus glycoproteins applied to subunit vaccine development.

AIMS: Vaccines for bovine ephemeral fever virus (BEFV) are available but are difficult to produce, expensive or suffer from genetic instability. Therefore, we designed constructs encoding C-terminally truncated forms (transmembrane anchoring region deleted) of glycoproteins G and GNS such that they were secreted from the cell into the media to achieve high-level antigen expression, correct glycosylation pattern and enable further simple purification with the V5 epitope tag. METHODS AND RESULTS: In this study, synthetic biology was employed to create membrane-bound and secreted forms of G and GNS glycoprotein. Mammalian cell culture was employed as an antigen expression platform, and the secreted forms of G and GNS protein were easily purified from media using a highly effective, single-step method. The V5 epitope tag was genetically fused to the C-termini of the proteins, enabling detection of the antigen through immunoblotting and immunomicroscopy. Our data demonstrated that the C-terminally truncated form of the G glycoprotein was efficiently secreted from cells into the cell media. Moreover the immunogenicity was confirmed in mice test. CONCLUSIONS: The immuno-dot blots showed that the truncated G glycoprotein was present in the total cell extract, and was clearly secreted into the media, consistent with the western blotting data and live-cell images. Our strategy presented the expression of secreted, epitope-tagged, forms of the BEFV glycoproteins such that appropriately glycosylated forms of BEFV G protein was secreted from the BHK-21 cells. This indicates that high-level expression of secreted G glycoprotein is a feasible strategy for large-scale production of vaccines and improving vaccine efficacy. SIGNIFICANCE AND IMPACT OF THE STUDY: The antigen expression strategy designed in this study can produce high-quality recombinant protein and reduce the amount of antigen used in the vaccine.

Increasing mitigation ambition to meet the Paris Agreement's temperature goal avoids substantial heat-related mortality in U.S. cities.

Current greenhouse gas mitigation ambition is consistent with ~3°C global mean warming above preindustrial levels. There is a clear need to strengthen mitigation ambition to stabilize the climate at the Paris Agreement goal of warming of less than 2°C. We specify the differences in city-level heat-related mortality between the 3°C trajectory and warming of 2° and 1.5°C. Focusing on 15 U.S. cities where reliable climate and health data are available, we show that ratcheting up mitigation ambition to achieve the 2°C threshold could avoid between 70 and 1980 annual heat-related deaths per city during extreme events (30-year return period). Achieving the 1.5°C threshold could avoid between 110 and 2720 annual heat-related deaths. Population changes and adaptation investments would alter these numbers. Our results provide compelling evidence for the heat-related health benefits of limiting global warming to 1.5°C in the United States.

Corrigendum: Detecting sulphate aerosol geoengineering with different methods.

This corrects the article DOI: 10.1038/srep39169.

Detecting sulphate aerosol geoengineering with different methods.

Sulphate aerosol injection has been widely discussed as a possible way to engineer future climate. Monitoring it would require detecting its effects amidst internal variability and in the presence of other external forcings. We investigate how the use of different detection methods and filtering techniques affects the detectability of sulphate aerosol geoengineering in annual-mean global-mean near-surface air temperature. This is done by assuming a future scenario that injects 5 Tg yr-1 of sulphur dioxide into the stratosphere and cross-comparing simulations from 5 climate models. 64% of the studied comparisons would require 25 years or more for detection when no filter and the multi-variate method that has been extensively used for attributing climate change are used, while 66% of the same comparisons would require fewer than 10 years for detection using a trend-based filter. This highlights the high sensitivity of sulphate aerosol geoengineering detectability to the choice of filter. With the same trend-based filter but a non-stationary method, 80% of the comparisons would require fewer than 10 years for detection. This does not imply sulphate aerosol geoengineering should be deployed, but suggests that both detection methods could be used for monitoring geoengineering in global, annual mean temperature should it be needed.

Role of tumor suppressor PTEN in tumor necrosis factor alpha-induced inhibition of insulin signaling in murine skeletal muscle C2C12 cells.

In an attempt to clarify the role of phosphatase and tensin homologue deleted on chromosome 10 (PTEN) in muscle insulin resistance, we investigated the effect of PTEN on phosphoinositide 3 (PI3)-kinase/Akt related insulin signaling pathway in skeletal muscle-like C2C12 cells damaged by tumor necrosis factor-alpha (TNFalpha). C2C12 cells cultured with TNFalpha (10 ng/ml) for 1 h displayed a marked decrease of insulin-stimulated 2-[14C]-deoxy-D-glucose (2-DG) uptake in parallel with an elevation of PTEN mRNA and protein levels. However, pretreatment of PTEN antisense oligonucleotide (AS) (1 micromol/l for 3 days) for specific inhibition of PTEN expression in C2C12 cells abolished the TNFalpha-induced changes in 2-DG uptake. Similar pretreatment with PTEN AS, but not with sense oligonucleotide (1 micromol/l for 3 days), eliminated the ability of TNFalpha to impair insulin-stimulated signals including p85 regulatory subunit of PI3-kinase expression and the degree of Akt serine phosphorylation as well as protein expression in glucose transporter subtype 4. Data taken from cultured C2C12 cells emphasize the negative regulatory of muscle PI3-kinase/Akt signaling pathways as the major substrate of PTEN but also support the concept that PTEN contributes to the development of insulin resistance in skeletal muscle.

Increase of PTEN gene expression in insulin resistance.

Phosphatase and tensin homologue deleted from chromosome ten (PTEN) has recently been characterized as a regulator of insulin sensitivity in the insulin target tissue. However, whether PTEN gene expression is changed in insulin resistance remains unclear. We observed that both the mRNA and protein level of PTEN in soleus muscle isolated from the obese Zucker rats (Fa/Fa) were increased compared to the age-matched lean group. Similarly, both the mRNA and protein level of PTEN in soleus muscle of the fructose-fed lean Zucker rats (Fa/Fa) showing the higher glucose-insulin index were higher than that of the regular chow fed group. These results suggest that increase of PTEN gene expression seems to be related to the development of insulin resistance.

Anomalies of dielectric-coated gratings.

Experimental results at millimeter wavelengths on dielectric-coated gratings are reported that show sharp anomalous dips in the transmission intensity for both P and S polarizations (i.e., incident electric field parallel and perpendicular to the slits, respectively). These dips almost disappear when either the dielectric is removed or the slits are randomly spaced. Next, a theory is developed for the gratings of finite extent and nonuniform spacings. Theoretical results, although approximate, agree remarkably well with the experiment.